Long-Term Effects of Repeated Prefrontal Cortex Transcranial Direct Current Stimulation (tDCS) on Food Craving in Normal and Overweight Young Adults.

BACKGROUND: The dorsolateral prefrontal cortex (DLPFC) plays an important role in the regulation of food intake. Several previous studies demonstrated that a single session of transcranial direct current stimulation (tDCS) of the DLPFC reduces food craving and caloric intake. OBJECTIVES: We hypothesized that repeated tDCS of the right DLPFC cortex may exert long-term changes in food craving in young, healthy adults and that these changes may differ between normal and overweight subjects. METHODS: Thirty healthy individuals who reported frequent food cravings without a prior history of eating disorders were initially recruited. Subjects were randomized into an ACTIVE group who received 5 days of real tDCS (20 minutes, anode right-cathode left montage, 2 mA with current density kept at 0.06 mA/cm2, 1 min ramp-up/ramp-down), and a SHAM group, who received one day of real tDCS, on the first day (same parameters), followed by 4 days of sham tDCS. Food craving intensity was examined by Food Craving Questionnaires State and Trait and Food Craving Inventory before, during, (5-days) and one month (30-days) after tDCS. RESULTS: Single session of tDCS significantly reduced the intensity of current food craving (FCQ-S). Five days of active tDCS significantly reduced habitual experiences of food craving (FCQ-T), when compared to baseline pre-stimulation levels. Furthermore, both current (FCQ-S) and habitual craving (FCQ-T) were significantly reduced 30 days after active tDCS, while sham tDCS, i.e. a single tDCS session did not have significant effects. Also, active tDCS significantly decreased craving for fast food and sweets, and to a lesser degree for fat, while it did not have significant effects on craving for carbohydrates (FCI). There were no significant differences between individual FCQ-T subscales (craving dimensions) after 5 or 30 days of either sham or active tDCS. Changes in craving were not significantly associated with the initial weight, or with weight changes 30 days after the stimulation in the subjects. CONCLUSIONS: The results confirm earlier findings that single session of tDCS has immediate effects in reducing food craving. They also show that repeated tDCS over the right DLPFC may increase the duration of its effects, which may be present 30 days after the stimulation. These results support further investigation of the use of tDCS in obesity.

A novel BRD4-NUT fusion in an undifferentiated sinonasal tumor highlights alternative splicing as a contributing oncogenic factor in NUT midline carcinoma.

NUT midline carcinoma (NMC) is a fatal cancer that arises in various tissues along the upper midline of the body. The defining molecular feature of NMC is a chromosomal translocation that joins (in the majority of cases) the nuclear testis gene NUT (NUTM1) to the bromodomain protein family member 4 (BRD4) and thereby creating a fusion oncogene that disrupts cellular differentiation and drives the disease. In this study, we report the case of an adolescent NMC patient presenting with severe facial pain, proptosis and visual impairment due to a mass arising from the ethmoid sinus that invaded the right orbit and frontal lobe. Treatment involved radical resection, including exenteration of the affected eye with the view to consolidate treatment with radiation therapy; however, the patient experienced rapid tumor progression and passed away 79 days post resection. Molecular analysis of the tumor tissue identified a novel in-frame BRD4-NUT transcript, with BRD4 exon 15 fused to the last 124 nucleotides of NUT exon 2 (BRD4-NUT ex15:ex2Δnt1-585). The partial deletion of NUT exon 2 was attributed to a mid-exonic genomic breakpoint and the subsequent activation of a cryptic splice site further downstream within the exon. Inhibition of the canonical 3' acceptor splice site of NUT intron 1 in cell lines expressing the most common NMC fusion transcripts (PER-403, BRD4-NUT ex11:ex2; PER-624, BRD4-NUT ex15:ex2) induced alternative splicing from the same cryptic splice site as identified in the patient. Detection of low levels of an in-frame BRD4-NUT ex11:ex2Δnt1-585 transcript in PER-403 confirmed endogenous splicing from this alternative exon 2 splice site. Although further studies are necessary to assess the clinical relevance of the increasing number of variant fusions described in NMC, the findings presented in this case identify alternative splicing as a mechanism that contributes to this pathogenic complexity.

DW-MRI of liver lesions: can a single ADC-value represent the entire lesion?

AIM: To evaluate whether focal liver lesions (FLLs) exhibit a homogeneous appearance on apparent diffusion coefficient (ADC) maps and whether there is inter-section variation in the calculated ADC values of FLLs (inter-section range). MATERIALS AND METHODS: Eighty-eight patients with 128 FLLs (70 benign, 58 malignant) who underwent abdominal magnetic resonance imaging (MRI) including diffusion-weighted (DW)-MRI were included. Two observers evaluated variation of signal intensity of each FLL within each ADC map image (intra-section) and among different ADC map images through the lesion (inter-section). ADC values of each FLL and neighbouring liver parenchyma were measured on all sections. The inter-section range of FLLs was compared with the neighbouring liver parenchyma. RESULTS: Intra-section inhomogeneity was noted in 39.8% (97/244 sections) and 38.9% (95/244) of benign lesions, and 61% (114/187 sections) and 61.5% (115/187) of malignant lesions, by observer 1 and observer 2, respectively. Inter-section inhomogeneity was noted in 25.7% (18/70) and 27.1% (19/70) of benign lesions, and 51.7% (30/58) and 50% (29/58) of malignant lesions, by observer 1 and observer 2, respectively. The inter-section range for both benign (0.28 × 10(-3) mm(2)/s) and malignant (0.25 × 10(-3) mm(2)/s) FLLs were significantly greater than that of liver parenchyma surrounding benign (0.16 × 10(-3) mm(2)/s, p < 0.001) and malignant (0.14 × 10(-3) mm(2)/s, p = 0.01) FLLs. CONCLUSION: Due to intra-/inter-section variations in ADC values of benign and malignant FLLs, a single ADC value may not reliably represent the entire lesion.

The effect of single-pulse transcranial magnetic stimulation and peripheral nerve stimulation on complexity of EMG signal: fractal analysis.

The aim of this study was to examine whether single-pulse transcranial magnetic stimulation (spTMS) affects the pattern of corticospinal activity once voluntary drive has been restored after spTMS-induced EMG silence. We used fractal dimension (FD) to explore the 'complexity' of the electromyography (EMG) signal, and median frequency of the spectra (MDF) to examine changes in EMG spectral characteristics. FD and MDF of the raw EMG epochs immediately before were compared with those obtained from epochs after the EMG silence. Changes in FD and MDF after spTMS were examined with three levels of muscle contraction corresponding to weak (20-40%), moderate (40-60%) and strong (60-80% of maximal voluntary contraction) and three intensities of stimulation set at 10, 20 and 30% above the resting motor threshold. FD was calculated using the Higuchi fractal dimension algorithm. Finally, to discern the origin of FD changes between the CNS and muscle, we compared the effects of spTMS with the effects of peripheral nerve stimulation (PNS) on FD and MDF. The results show that spTMS induced significant decrease in both FD and MDF of EMG signal after stimulation. PNS did not have any significant effects on FD nor MDF. Changes in TMS intensity did not have any significant effect on FD or MDF after stimulation nor had the strength of muscle contraction. However, increase in contraction strength decreased FD before stimulation but only between weak and moderate contraction. The results suggest that the effects of spTMS on corticospinal activity, underlying voluntary motor output, outlast the TMS stimulus. It appears that the complexity of the EMG signal is reduced after spTMS, suggesting that TMS alters the dynamics of the ongoing corticospinal activity most likely temporarily synchronizing the neural network activity. Further studies are needed to confirm whether observed changes after TMS occur at the cortical level.

FBXO11, a regulator of the TGFß pathway, is associated with severe otitis media in Western Australian children.

Otitis media (OM) is a common childhood disease characterised by middle ear inflammation following infection. Susceptibility to recurrent acute OM (rAOM) and chronic OM with effusion (COME) is highly heritable. Two murine mutants, Junbo and Jeff, spontaneously develop severe OM with similar phenotypes to human disease. Fine-mapping of these mutants identified two genes (Evi1 and Fbxo11) that interact with the transforming growth factor ß (TGFß) signalling pathway. We investigated these genes, as well as four Sma- and Mad-related (SMAD) genes of the TGFß pathway, as candidate rAOM/COME susceptibility genes in two predominantly Caucasian populations. Single-nucleotide polymorphisms (SNPs) within FBXO11 (family-based association testing Z-Score=2.61; P(best)=0.009) were associated with severe OM in family-based analysis of 434 families (561 affected individuals) from the Western Australian Family Study of OM. The FBXO11 association was replicated by directed analysis of Illumina 660W-Quad Beadchip data available for 253 cases and 866 controls (OR=1.55 (95% CI 1.28-1.89); P(best)=6.9 × 10(-6)) available within the Western Australian Pregnancy Cohort (Raine) Study. Combined primary and replication results show P(combined)=2.98 × 10(-6). Neither cohort showed an association with EVI1 variants. Family-based associations at SMAD2 (P=0.038) and SMAD4 (P=0.048) were not replicated. Together, these data provide strong evidence for FBXO11 as a susceptibility gene for severe OM.

Recurrent postcardiac injury syndrome mimicking cardiac perforation following transvenous pacing: An unusual presentation.

We report a case of recurrent postcardiac injury syndrome (PCIS) after pacemaker lead insertion. Each episode was attended by hemorrhagic pleuro-pericardial effusion with drop in hemoglobin levels leading us to consider cardiac perforation and subject the patient to surgical pericardiotomy. However, no perforation or active bleeding was detected on exploration. This unusual case illustrates the occurrence of PCIS following pacemaker lead insertion, mimicking cardiac perforation. This entity should be considered in patients who, after pacemaker lead insertion, develop pericardial and pleural effusion associated with markers of inflammation.

A Kohonen-like decomposition method for the Euclidean traveling salesman problem-KNIES/spl I.bar/DECOMPOSE.

In addition to the classical heuristic algorithms of operations research, there have also been several approaches based on artificial neural networks for solving the traveling salesman problem. Their efficiency, however, decreases as the problem size (number of cities) increases. A technique to reduce the complexity of a large-scale traveling salesman problem (TSP) instance is to decompose or partition it into smaller subproblems. We introduce an all-neural decomposition heuristic that is based on a recent self-organizing map called KNIES, which has been successfully implemented for solving both the Euclidean traveling salesman problem and the Euclidean Hamiltonian path problem. Our solution for the Euclidean TSP proceeds by solving the Euclidean HPP for the subproblems, and then patching these solutions together. No such all-neural solution has ever been reported.

Discrete vector quantization for arbitrary distance function estimation.

There are currently many vastly different areas of research involving adaptive learning. Among them are the two areas that concern neural networks and learning automata. This paper develops a method by which the general philosophies of vector quantization (VQ) and discretized automata learning can be incorporated for the computation of arbitrary distance functions. The latter is a problem which has important applications in logistics and location analysis. The input to our problem is the set of coordinates of a large number of nodes whose internode arbitrary "distances" have to be estimated. To render the problem interesting, nontrivial, and realistic, we assume that the explicit form of this distance function is both unknown and uncomputable. Unlike traditional operations research methods, which use optimized parametric functional estimators, we have utilized discretized VQ principles to first adaptively polarize the nodes into subregions. Subsequently, the parameters characterizing the subregions are learned by using a variety of methods (including, for academic purposes, a VQ strategy in the meta-domain). After an initial training phase, a system which achieves distance estimation attempts to yield an estimate of any node-pair distance without actually deriving an explicit form for the unknown function. The algorithms have been rigorously tested for the actual road-travel distances involving cities in Turkey and the results obtained are conclusive. Indeed, these present results are the best currently available from any single or hybrid strategy.